Macitentan

Macitentan is a prescription medication used for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to reduce the risk of disease progression and hospitalization. 

• Macitentan is available under the following different brand names: Opsumit

Common side effects of Macitentan include:

• Low red blood cell count (anemia),

Common cold-like symptoms (stuffy nose or sore throat),

• Bronchitis,
• Headache,
• Flu and
• Urinary tract infection.

Serious side effects of Macitentan include:

• Dark urine, 
• Persistent nausea/vomiting/loss of appetite, 
• Stomach/abdominal pain, yellowing eyes/skin.
• Rash,
• Itching/swelling (especially of the face/tongue/throat), 
• Severe dizziness, and trouble breathing.

Rare side effects of Macitentan include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 10 mg

Pulmonary Arterial Hypertension

Adult dosage

• 10 mg orally once a day
• Higher doses have not been studied and are not recommended.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Macitentan has severe interactions with no other drugs.
• Macitentan has serious interactions with at least 48 other drugs.
• Macitentan has moderate interactions with the following drugs:
  • carbamate
  • duvelisib
  • elagolix
  • encorafenib
  • fedratinib
  • istradefylline
  • mitotane
  • rucaparib
  • stiripentol
  • tazemetostat
  • tecovirimat
• Macitentan has minor interactions with the following drug:
  • sildenafil

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• History of hypersensitivity reaction to drugs or excipients
• Pregnancy; consistently shown to have teratogenic effects in animal studies

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Macitentan?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Macitentan?”

Cautions

• If pulmonary edema occurs, consider the possibility of associated pulmonary venous-occlusive disease, and if confirmed, discontinue the drug
• Decreases in hemoglobin concentration and hematocrit reported; decreases in hemoglobin seldom require transfusion; initiation of therapy is not recommended in patients with severe anemia; measure hemoglobin before initiation of treatment and repeat during treatment as clinically indicated

Hepatotoxicity

• Other endothelin receptor antagonists (ERAs) have been associated with elevated liver aminotransferases, hepatotoxicity, and liver failure
• Obtain liver enzymes tests before initiating and repeat as clinically warranted
• Discontinue if aminotransferase elevations are accompanied by clinical symptoms of hepatoxicity
• Advise patients to report symptoms suggesting hepatic injury (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching)
• If clinically relevant aminotransferase elevations occur, or if elevations are accompanied by an increase in bilirubin above 2 for ULN, or by clinical symptoms of hepatotoxicity, discontinue therapy
• Consider re-initiation of therapy when hepatic enzyme levels normalize in patients who have not experienced clinical symptoms of hepatotoxicity

Fluid retention

• Patients with underlying left ventricular dysfunction may be at particular risk for developing significant fluid retention after initiation of ERA treatment
• Postmarketing cases of edema and fluid retention occurring within weeks of starting therapy, some requiring intervention with a diuretic or hospitalization for decompensated heart failure, reported
• Monitor for signs of fluid retention after initiating therapy; if clinically significant fluid retention develops, evaluate the patient to determine the cause, such as the therapy being administered or underlying heart failure, and the possible need to discontinue therapy

Drug interaction overview

• Macitentan is a CYP3A4 substrate
• Strong CYP3A4 inducers significantly reduce macitentan systemic exposure; avoid coadministration
• Avoid coadministration with strong CYP3A4 inhibitors, as macitentan systemic exposure is approximately doubled; use other PAH treatment options when CYP3A4 inhibitors are needed as part of HIV treatment
• Moderate dual or combined CYP3A4 and CYP2C9 inhibitors
• Concomitant use of moderate dual inhibitors of CYP3A4 and CYP2C9 such as fluconazole is predicted to increase macitentan exposure approximately 4-fold based on physiologically based pharmacokinetic (PBPK) modeling; avoid concomitant use of the drug with moderate dual inhibitors of CYP3A4 and CYP2C9 (such as fluconazole and amiodarone)
• Concomitant treatment of both a moderate CYP3A4 inhibitor and a moderate CYP2C9 inhibitor with macitentan should also be avoided.

Pregnancy and Lactation

• Based on data from animal reproduction studies, therapy may cause embryo-fetal toxicity, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy; there are risks to the mother and fetus associated with pulmonary arterial hypertension in pregnancy; there are limited data on use in pregnant women; the drug was teratogenic in rabbits and rats at all doses tested; if the drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of risk to a fetus
• In patients with pulmonary arterial hypertension, pregnancy is associated with an increased rate of maternal and fetal morbidity and mortality, including spontaneous abortion, intrauterine growth restriction, and premature labor
• Pregnancy testing
  • Verify the pregnancy status of females of reproductive potential before initiating therapy, monthly during treatment, and one month after stopping treatment; the patient should contact her physician immediately for pregnancy testing if the onset of menses is delayed or pregnancy is suspected; if the pregnancy test is positive, the physician and patient must discuss risks to her, the pregnancy, and fetus
• Contraception
  • Female patients of reproductive potential must use acceptable methods of contraception during treatment and for 1 month after stopping
  • Patients may choose 1 highly effective form of contraception (intrauterine devices [IUD], contraceptive implants, or tubal sterilization) or a combination of methods (hormone method with a barrier method or 2 barrier methods)
  • If a partner’s vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method
• Infertility
  • Based on findings in animals, the drug may impair fertility in males of reproductive potential; not known whether the effects on fertility would be reversible
  • Therapy may hurt spermatogenesis, counsel men about potential effects on fertility
• Lactation
  • There are no data on the presence of macitentan in human milk, its effects on the breastfed infant, or milk production; because of the potential for serious adverse reactions in breastfed infants advise women not to breastfeed during treatment